As the process for producing a compound of the general formula [1], there has been known the process described in WO97/29102. That is to say, said publication describes that a compound of the general formula [1] can be produced by subjecting a 5-halogenoisoindoline derivative represented by the following general formula [4] or its salt:
wherein R3, R4 and R5 have the same meanings as mentioned above and X1 represents a halogen atom, to lithiation or Grignard reaction and thereafter to reaction with a trialkyl borate to form an isoindoline-5-boronic acid derivative represented by the following general formula [2c] or its salt:
wherein R3, R4 and R5 have the same meanings as mentioned above and R11 represents a hydrogen atom or an alkyl group; and subsequently reacting the isoindoline-5-boronic acid derivative or its salt with a 7-halogenoquinolonecarboxylic acid represented by the following general formula [3b]:
wherein R1, R2, R6 and A have the same meanings as mentioned above and X3 represents a halogen atom, in the presence of a palladium complex such as bis(triphenylphosphine)-palladium(II) chloride, tetrakis(triphenylphosphine)-palladium(0) or the like.
Among the compounds of the general formula [1], (R)-1-cyclopropyl-8-difluoromethoxy-7-(1-methyl-2,3-dihydro-1H-5-isoindolyl)-4-oxo-1,4-dihydro-3-quinoline-carboxylic acid represented by the formula:
(referred to hereinafter as T-3811) is a compound excellent in activity against Gram-positive and Gram-negative bacteria and the development of a process for industrially producing the same has been desired.
Moreover, T-3811 is low in solubility in the vicinity of neutral, so that the enhancement of solubility at a physiologically acceptable pH has been desired.